Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in Vitro and in Vivo

Martina Schmidl, Nadia Adam, Cordula Surmann-Schmitt, Takako Hattori, Michael Stock, Uwe Dietz, Benoit De Crombrugghe, Ernst Pöschl, Klaus Von Der Mark

Research output: Contribution to journalArticle

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Abstract

Twisted gastrulation (TSG) is an extracellular modulator of bone morphogenetic protein (BMP) activity and regulates dorsoventral axis formation in early Drosophila and Xenopus development. Studies on tsg-deficient mice also indicated a role of this protein in skeletal growth, but the mechanism of TSG activity in this process has not yet been investigated. Here we show for the first time by in situ hybridization and immunohistochemistry that TSG is strongly expressed in bovine and mouse growth plate cartilage as well as in fetal ribs, vertebral cartilage, and cartilage anlagen of the skull. Furthermore we provide evidence that TSG is directly involved in BMP-regulated chondrocyte differentiation and maturation. In vitro, TSG impaired the dose-dependent BMP-2 stimulation of collagen II and X expression in cultures of MC615 chondrocytes and primary mouse chondrocytes. In the presence of chordin, a BMP antagonist, the inhibitory effect of TSG was further enhanced. TSG also inhibited BMP-2-stimulated phosphorylation of Smad factors in chondrocytes, confirming the role of TSG as a modulator of BMP signaling. For analysis of TSG functions in cartilage development in vivo, the gene was overexpressed in transgenic mice under the control of the cartilage-specific Col2a1 promoter. As a result, Col10a1 expression was significantly reduced in the growth plates of transgenic embryos and newborns in comparison with wild type littermates as shown by in situ hybridization and by real time PCR analysis. The data suggest that TSG is an important modulator of BMP-regulated cartilage development and chondrocyte differentiation.

Original languageEnglish
Pages (from-to)31790-31800
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number42
DOIs
Publication statusPublished - Oct 20 2006

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Gastrulation
Bone Morphogenetic Proteins
Cartilage
Chondrocytes
Collagen
Modulators
Bone Morphogenetic Protein 2
Growth Plate
Phosphorylation
In Situ Hybridization
In Vitro Techniques
Genes
Ribs
Xenopus
Skull
Transgenic Mice
Drosophila
Real-Time Polymerase Chain Reaction
Embryonic Structures
Immunohistochemistry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in Vitro and in Vivo. / Schmidl, Martina; Adam, Nadia; Surmann-Schmitt, Cordula; Hattori, Takako; Stock, Michael; Dietz, Uwe; De Crombrugghe, Benoit; Pöschl, Ernst; Von Der Mark, Klaus.

In: Journal of Biological Chemistry, Vol. 281, No. 42, 20.10.2006, p. 31790-31800.

Research output: Contribution to journalArticle

Schmidl, M, Adam, N, Surmann-Schmitt, C, Hattori, T, Stock, M, Dietz, U, De Crombrugghe, B, Pöschl, E & Von Der Mark, K 2006, 'Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in Vitro and in Vivo', Journal of Biological Chemistry, vol. 281, no. 42, pp. 31790-31800. https://doi.org/10.1074/jbc.M603419200
Schmidl, Martina ; Adam, Nadia ; Surmann-Schmitt, Cordula ; Hattori, Takako ; Stock, Michael ; Dietz, Uwe ; De Crombrugghe, Benoit ; Pöschl, Ernst ; Von Der Mark, Klaus. / Twisted gastrulation modulates bone morphogenetic protein-induced collagen II and X expression in chondrocytes in Vitro and in Vivo. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 42. pp. 31790-31800.
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